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Biochem & Cell bio > unit 18 : glucose metabolism > Flashcards

unit 18 : glucose metabolism Flashcards

1
Q

Name the order of enzymes in glycolysis

A

hexokinase
phosphoglucose isomerase
PFK (phosphofructose kinase-1)
Aldolase
Triose phosphate isomerase
Glyceraldehyde 3-phosphate dehydrogenase
phosphoglycerate kinase
phosphoglyceromutase
enolase
pyruvate kinase

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2
Q

Name the reaction products in glycolysis (in order)

A

Glucose 6-phosphate
Fructose 6-phosphate
Fructose 1, 6-bisphosphate
DHAP and Glyceraldehyde 3-phosphate *G3P is the only product that can move forward (this part happens twice)
1,3-bisphosphoglycerate
3-phosphoglycerate
2-phosphoglycerate
Phosphoenolpyruvate
Pyruvate

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3
Q

what are the irreversible steps of glycolysis

A

step 1 (hexokinase)
step 3 (PFK-1)
step 10 (Pyruvate kinase)

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4
Q

what steps require ATP and what steps produce it

A

require/investment:
Step 1 (hexokinase
Step 3 (PFK-1)

produce it:
step 7 (phosphoglycerate kinase)
step 10 (pyruvate kinase)

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5
Q

oxidation/reduction steps

A

step 7: NAD is reduced to NADH and glyceraldehyde 3- phosphate is oxidized to 1,3-BPG
STEP 9: H2O is produced

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6
Q

enzymes required to digest dietary carbs

A

a-amylase
a-glucosidase
a- dextrinase (isomaltase)
maltase
sucrase
lactase

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7
Q

Allosteric regulation of muscle PFK-1:

A

inhibited by high ATP
- lowers affinity to F6P

activated by high levels of AMP

Inhibition by ATP greater at lower pH
(muscle isoform only)
– Reduces further accumulation of excess acids in muscle

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8
Q

Allosteric Regulation of Liver PFK

A

Regulated by energy charge
– Inhibited by ATP
– Activated by AMP

Inhibited by citrate (TCA cycle)

Activated by Fructose 2,6-bis-P
– Produced by PFK-2 at high blood glucose levels
– Reduces inhibitory effect of ATP
– Increases affinity for fructose 6-P
example of Feedforward activation

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9
Q

Effects of glucagon and insulin on PFK-1 in liver

A

-glucagon deactivates PFK-1
- insulins activates PFK-1

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10
Q

Allosteric Regulation of Hexokinase

A
  • high levels of G6P inhibit
  • Indirect control by phosphofructokinase activity
    – Accumulation of fructose 6-P by low PFK-1 activity leads to reversible conversion to Glucose 6-P
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11
Q

describe hexokinase isoenzymes

A
  • 4 different isozymes in humans
  • G6P inhibits I, II, III, but not IV (glucokinase a liver isoform)
    • Allows high levels of glucose 6P in liver
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12
Q

there are different Km’s for Hexokinase of glucose?

A

true
– Hexokinase I: KM~ 0.2 mM
– Hexokinase IV: KM ~ 10 mM

** Significant activity only at very high glucose concentrations

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13
Q

allosteric regulation of pyruvate kinase

A
  • inhibited by high levels of ATP, acetyl Co-A and alanine

high acetyl-coa concentration says there’s a lot of energy and TCA is backed up
alanine is a derivative of pyruvate. it indicates high pyruvate concentration

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14
Q

Control of Glycolysis by Compartmentalization

A
  • Uptake of glucose from blood by passive transport
  • several glucose transporter (GLUT) Isoforms with different KM

– GLUT1 (most cells): KM ~3mM < typical concentration in blood
- Active even at low blood glucose levels

– GLUT2 (liver, pancreas): KM ~20 mM&raquo_space; typical concentration in blood
- Active only at high blood glucose levels;
- Removes excess glucose when glucose levels are high
- Low activity at low blood glucose levels prevents ‘syphoning’ off glucose from brain and muscles at fasting conditions
- Increased expression in cancer cells

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15
Q

Regulation of Glycolysis by Transcriptional Control

A

Regulate expression of glycolytic enzymes
– Glucokinase
– PFK-1
– Pyruvate kinase

regulated by hormones insulin and glucagon

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16
Q

describe bypassing step 10 in gluconeogenesis

A

Pyruvate carboxylase rxn
- Pyruvate transported into mitochondria
- converted from C3 to C4 in mitochondria by carboxylation

  • Biotin used as prosthetic group
    – Driven by ATP cleavage
    – Allosteric activation by acetyl-CoA

PEP carboxykinase rxn
- occurs in cytoplasm
- Shuttling of oxaloacetate to Cytoplasm via malate-aspartate shuttle

17
Q

describe Bypassing Step 3 in gluconeogenesis

A

-Fructose 1,6-BP converted to F6P by fructose 1,6-bisphophatase
- hydrolysis rxn
- Regulatory function in gluconeogenesis
–Inhibited by Fruc 2,6-BP

18
Q

describe bypassing step 1 in gluconeogenesis

A
  • Glucose 6-P converted to glucose by glucose 6-phosphatase
  • occurs in ER lumen
19
Q

gluconeogenesis rxn

A

2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H + 2 H2O = Glucose + 4 ADP + 4 Pi + 2 NAD+

6 NTPs consumed (net)

20
Q

allosteric regulation of gluconeogenesis

A

Fructose 1,6-BP:
inhibited by high levels of AMP and F 2,6-BP

Pyruvate carboxylase
activated by acetyl-CoA

21
Q

Control of Blood Glucose Level by Liver - High Blood Glucose

A
  • Increased uptake by additional glucose transporter (GLUT2)

Increased rate of glycolysis and glycogen synthesis
– Inhibition of glycogen phosphorylase

Decreased gluconeogenesis
– Increased F 2,6BP

22
Q

Control of Blood Glucose Level by Liver – Low Blood Glucose

A
  • Increased glycogenolysis
    and gluconeogenesis
    – precursors: Lactate, glucogenic amino acids, glycerol
  • Reduced glycolysis due to lower levels of fructose 2,6-BP
    -Hydrolysis of glucose 6P by phosphatase to glucose
  • GLUT2 releases glucose into blood
23
Q

Phases of Pentose Phosphate Pathway

A

oxidative phase
- provides NADPH in 2 oxidation steps
- converts G6P to ribulose 5P
- irreversible rxns
- regulated

non oxidative phase
- converts ribulose 5P to other sugars
- Ribose 5P
- Fructose 5P, GA3P or other sugars
- reversible

24
Q

net reaction of the oxidative phase of PPP

A

G6P + 2 NADP+ + H2O = Ribulose5P + 2 NADPH + H + CO2

25
Q

what do transketolases do and transaldolases do?

A

transketolases move 2 carbons

transaldolases move 3 carbons

26
Q

what are the main reactions of the oxidative phase of PPP

A
  • Glucose-6 phosphate dehydrogenase
  • 6-phosphogluconate dehydrogenase
27
Q

enzymes involved in non oxidative phase of PPP

A

– Transketolase
– Transaldolase
– Isomerases - rearranges a molecules
– Epimerases- changes the arrangement of one carbon

28
Q

regulation of PPP

A

Glucose 6P DH inhibited by NADPH
- Low NADPH/NADP+ ratio
→ flux of Glucose 6P into PP pathway
– High NADPH/NAD+ ratio
→ reduced flux of Glucose 6P into PP pathway and increased flux into glycolysis. need ATP instead

Non-oxidative phase reactions reversible
– Controlled by substrate availability

29
Q

what is the role of NADPH in ROS detoxification

A

Glutathione is an important ROS Scavenger
- NADPH reduces GSSG
- regenerates by reducing GSSG to GSH

reaction goes from
GSH + H2O2 = GSSG + 2 H2O via glutathione peroxidase

30
Q

what is the purpose of the PPP

A
  • produce NADPH and Ribulose 5-phosphate
  • NADPH produces reducing power for biosynthesis
  • Ribulose 5-phosphate for nucleic acid synthesis

Biochem & Cell bio (20 decks)

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